Schistosoma mansoni, a human blood fluke parasite, causes a disease of major health importance in many parts of the worlds. The eggs produced in large number by the adult worms of this organism are the primary causes of the pathology of the disease. The eggs have two fates, one, to penetrate through the tissues of the host, eventually to be passed out of the host by way of the feces, and two, to fail to penetrate fully the host tissues and to become trapped. The trapped eggs elicit an immune response leading to fibrosis within host tissues. The eggs which pass out of the host can hatch to yield a miracidium which can penetrate the intermediate snail host and continue the life cycle. We have been interested in the proteolytic enzymes of Schistosoma mansoni eggs in order to determine whether such enzymes might play a role in either or both of the two fates of the schistosome eggs. The first aim of this project is to isolate, characterize, and compare the proteolytic enzymes in extracts and secretions of Schistosoma mansoni eggs and miracidia. In addition, these enzymes will be compared with a related thiol proteinase from adult worms. The physical and enzymatic properties of the enzymes will be determined. The role of these enzymes in host tissue penetration will be tested using purified connective tissue components. The second aim of this project is to utilize monoclonal antibodies to localize the enzymes in the schistosome egg and in host tissues, so as to study the relationship of these enzymes to antigens that elicit the host's immune responses. In addition, these antibodies will be utilized to clone the gene for the egg proteinase in Escherichia coli, so as to allow us to amplify production of the proteinase, and to obtain insight into the genetic organization of these enzymes. The ability of these antibodies to protect against challenge infection will be tested.